ACVR2B

Summary

ACVR2B (activin A receptor type 2B, HGNC:174) is a protein-coding gene on chromosome 3p22.2, encoding Activin receptor type-2B (Q13705). Transmembrane serine/threonine kinase activin type-2 receptor forming an activin receptor complex with activin type-1 serine/threonine kinase receptors (ACVR1, ACVR1B or ACVR1c).

Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I (I and IB) and two type II (II and IIB) receptors. These receptors are all transmembrane proteins, composed of a ligand-binding extracellular domain with cysteine-rich region, a transmembrane domain, and a cytoplasmic domain with predicted serine/threonine specificity. Type I receptors are essential for signaling; and type II receptors are required for binding ligands and for expression of type I receptors. Type I and II receptors form a stable complex after ligand binding, resulting in phosphorylation of type I receptors by type II receptors. Type II receptors are considered to be constitutively active kinases. This gene encodes activin A type IIB receptor, which displays a 3- to 4-fold higher affinity for the ligand than activin A type II receptor.

Source: NCBI Gene 93 — RefSeq curated summary.

At a glance

• Gene–disease (curated): heterotaxy, visceral, 4, autosomal (Strong, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 381 total — 2 likely-pathogenic
• Phenotypes (HPO): 17
• Druggable target: yes — 12 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001106

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:174
Approved symbol	ACVR2B
Name	activin A receptor type 2B
Location	3p22.2
Locus type	gene with protein product
Status	Approved
Aliases	ActR-IIB
Ensembl gene	ENSG00000114739
Ensembl biotype	protein_coding
OMIM	602730
Entrez	93

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 retained_intron

ENST00000352511, ENST00000461232, ENST00000465020, ENST00000922132

RefSeq mRNA: 1 — MANE Select: NM_001106 NM_001106

CCDS: CCDS2679

Canonical transcript exons

ENST00000352511 — 11 exons

Exon	Start	End
ENSE00001861259	38453890	38454374
ENSE00003484673	38477287	38477494
ENSE00003500317	38482198	38482336
ENSE00003530637	38478375	38478518
ENSE00003549324	38479128	38479271
ENSE00003580976	38482430	38482560
ENSE00003586220	38481351	38481465
ENSE00003604962	38479678	38479826
ENSE00003648414	38478141	38478292
ENSE00003657582	38477861	38477970
ENSE00003676114	38483138	38493142

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 96.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.8621 / max 97.0665, expressed in 1238 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36104	4.4729	1096
36105	1.9964	593
202725	0.3928	199

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.45	gold quality
oocyte	CL:0000023	93.10	gold quality
ganglionic eminence	UBERON:0004023	88.03	gold quality
endothelial cell	CL:0000115	87.72	gold quality
parotid gland	UBERON:0001831	86.84	silver quality
ventricular zone	UBERON:0003053	86.40	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	85.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.33	gold quality
biceps brachii	UBERON:0001507	85.30	gold quality
pigmented layer of retina	UBERON:0001782	85.09	gold quality
lateral nuclear group of thalamus	UBERON:0002736	84.42	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	83.85	silver quality
lateral globus pallidus	UBERON:0002476	83.73	gold quality
embryo	UBERON:0000922	83.53	gold quality
subthalamic nucleus	UBERON:0001906	83.40	silver quality
cortical plate	UBERON:0005343	83.20	gold quality
heart right ventricle	UBERON:0002080	83.16	silver quality
bronchial epithelial cell	CL:0002328	83.03	gold quality
paraflocculus	UBERON:0005351	82.99	silver quality
substantia nigra pars reticulata	UBERON:0001966	82.97	silver quality
globus pallidus	UBERON:0001875	82.69	gold quality
ventral tegmental area	UBERON:0002691	82.52	gold quality
endometrium epithelium	UBERON:0004811	82.25	gold quality
medial globus pallidus	UBERON:0002477	82.18	gold quality
inferior vagus X ganglion	UBERON:0005363	82.13	gold quality
caput epididymis	UBERON:0004358	82.07	gold quality
superior vestibular nucleus	UBERON:0007227	81.88	gold quality
middle temporal gyrus	UBERON:0002771	81.87	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.71	gold quality
body of tongue	UBERON:0011876	81.63	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	2008.50
E-ANND-3	no	4.73

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
HAMP	Repression

miRNA regulators (miRDB)

451 targeting ACVR2B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-98-3P	100.00	74.08	3907
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181D-5P	99.99	73.04	2997

Literature-anchored findings (GeneRIF, showing 26)

• distribution in gestational tissues across human pregnancy and during labour (PMID:11969340)
• analysis of expression and cellular compartmentalization of the activin receptors ActRIIA, ActRIIB and ActRIB, the inhibin co-receptor (betaglycan), and activin signaling proteins Smads 2, 3 and 4, and growth regulatory role during lactation (PMID:12782414)
• Data indicate that activin A and activin receptors IIA and IIB may be involved in the regulation of germ cell proliferation in the human ovary during the period leading up to primordial follicle formation. (PMID:14738881)
• activin signaling via type II receptors requires a specific sequence for ALK4 binding (PMID:15123686)
• These results indicate that haplotype structure at the ACVR2B and follistatin loci may contribute to interindividual variation in skeletal muscle mass and strength, although these data indicate sex-specific relationships. (PMID:17347381)
• The high-resolution structure of human ActRIIB kinase domain in complex with adenine establishes the conserved bilobal architecture consistent with all other catalytic kinase domains. (PMID:17893364)
• Inhibition of negative regulators of skeletal muscle by a soluble form of activin type IIB receptor (ACE-031) increases muscle mass independent of fiber-type expression. (PMID:20466801)
• discussion of crystal structure of kinase domain of ActRIIB; structural analysis may be of help in developing selective inhibitors [REVIEW] (PMID:21353874)
• Mutations in Activin A Receptor Type IIB were identified in 4 of the 47 patients (8.5%) with heterotaxy syndrome. Our results expand the mutation spectrum of monogenic heterotaxy syndrome with associated cardiac anomalies. (PMID:21864452)
• Activin type IIB receptors are clearly demonstrable throughout the adult human hypothalamus and basal forebrain. (PMID:22296042)
• After eccentric exercise, postmenopausal women not using hormone therapy (HT) expressed lower levels of ActRIIb while postmenopausal women using HT showed a heightened response. (PMID:22395277)
• The interaction between all five miRNAs and ACVR2B was verified by an in vitro assay. (PMID:22431721)
• We found that the AAAAA, AGGAG, and AGGGA haplotypes in ACVR2B were associated with susceptibility to Premature Ovarian Failure when they also had at least one CATAG haplotype in ADAMTS19. (PMID:25051287)
• miR-21 interacts directly with the 3’-untranslated region of ACVR2B mRNA. Mechanical stretch suppressed ACVR2B protein levels in periodontal ligament stem cells. Gain- and loss of function of ACVR2B mediated the osteogenic differentiation of PDLSCs. (PMID:25203845)
• Activin A inhibited signaling by BMP-6 and BMP-9 by competing for type 2 receptors ACVR2A and ACVR2B. (PMID:26047946)
• Adenomyotic tissues express high levels of myostatin, follistatin, and activin type II receptors. (PMID:26086422)
• ActR-IIB is expressed in male germ cells and Sertoli cells. (PMID:26289399)
• the A allele of genetic variant rs2276541 in ACVR2B is associated with lean muscle mass (PMID:26848890)
• TGF-beta receptor mediated telomerase inhibition, telomere shortening and breast cancer cell senescence.( (PMID:27696331)
• MicroRNA-194 protects against chronic hepatitis B-related liver damage by promoting hepatocyte growth via ACVR2B. (PMID:30044042)
• Study supported ACVR2B as the facilitator for clear cell kidney carcinoma (KIRC) development. Its up-regulation controls the growth, viability, and EMT-specific protein expressions of KIRC cells. (PMID:30334578)
• Activation of activin receptor-2B by myostatin modulates the fibrogenic phenotype of human stellate cells, indicating that a myokine may be implicated in the pathogenesis of hepatic fibrosis. (PMID:31005555)
• Effects of Roux-en-Y gastric bypass on circulating follistatin, activin A, and peripheral ActRIIB signaling in humans with obesity and type 2 diabetes. (PMID:32873911)
• Activin A and Acvr2b mRNA from Umbilical Cord Blood Are Not Reliable Markers of Mild or Moderate Neonatal Hypoxic-Ischemic Encephalopathy. (PMID:33706404)
• Deficiency of myostatin protects skeletal muscle cells from ischemia reperfusion injury. (PMID:34131275)
• The association between sarcopenia susceptibility and polymorphisms of FTO, ACVR2B, and IRS1 in Tibetans. (PMID:34302448)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	acvr2ba	ENSDARG00000044422
danio_rerio	acvr2bb	ENSDARG00000103108
mus_musculus	Acvr2b	ENSMUSG00000061393
rattus_norvegicus	Acvr2b	ENSRNOG00000014477

Paralogs (11): TGFBR1 (ENSG00000106799), BMPR1A (ENSG00000107779), ACVR1 (ENSG00000115170), ACVR2A (ENSG00000121989), ACVR1C (ENSG00000123612), AMHR2 (ENSG00000135409), ACVR1B (ENSG00000135503), BMPR1B (ENSG00000138696), ACVRL1 (ENSG00000139567), TGFBR2 (ENSG00000163513), BMPR2 (ENSG00000204217)

Protein

Protein identifiers

Activin receptor type-2B — Q13705 (reviewed: Q13705)

Alternative names: Activin receptor type IIB

All UniProt accessions (1): Q13705

UniProt curated annotations — full annotation on UniProt →

Function. Transmembrane serine/threonine kinase activin type-2 receptor forming an activin receptor complex with activin type-1 serine/threonine kinase receptors (ACVR1, ACVR1B or ACVR1c). Transduces the activin signal from the cell surface to the cytoplasm and is thus regulating many physiological and pathological processes including neuronal differentiation and neuronal survival, hair follicle development and cycling, FSH production by the pituitary gland, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. Activin is also thought to have a paracrine or autocrine role in follicular development in the ovary. Within the receptor complex, the type-2 receptors act as a primary activin receptors (binds activin-A/INHBA, activin-B/INHBB as well as inhibin-A/INHA-INHBA). The type-1 receptors like ACVR1B act as downstream transducers of activin signals. Activin binds to type-2 receptor at the plasma membrane and activates its serine-threonine kinase. The activated receptor type-2 then phosphorylates and activates the type-1 receptor. Once activated, the type-1 receptor binds and phosphorylates the SMAD proteins SMAD2 and SMAD3, on serine residues of the C-terminal tail. Soon after their association with the activin receptor and subsequent phosphorylation, SMAD2 and SMAD3 are released into the cytoplasm where they interact with the common partner SMAD4. This SMAD complex translocates into the nucleus where it mediates activin-induced transcription. Inhibitory SMAD7, which is recruited to ACVR1B through FKBP1A, can prevent the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. Activin signal transduction is also antagonized by the binding to the receptor of inhibin-B via the IGSF1 inhibin coreceptor.

Subunit / interactions. Forms an activin receptor complex with activin type II receptors such as ACVR1B. Interacts with VPS39. Interacts with DYNLT1. Interacts with BMP3. Interacts with BMP2. Interacts with BMP6.

Subcellular location. Cell membrane.

Post-translational modifications. Phosphorylated. Constitutive phosphorylation is in part catalyzed by its own kinase activity.

Disease relevance. Heterotaxy, visceral, 4, autosomal (HTX4) [MIM:613751] A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. HTX4 clinical features include dextrocardia, right aortic arch and a right-sided spleen, anomalies of the inferior and the superior vena cava, atrial ventricular canal defect with dextro-transposed great arteries, pulmonary stenosis, polysplenia and midline liver. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Produced from the insertion in the transcript of 82 base pairs, leading to frameshift and protein truncation. May be not functional.

Similarity. Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13705-1	ActR-IIB2	yes
Q13705-2	ActR-IIB1

RefSeq proteins (1): NP_001097* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000333	TGFB_receptor	Family
IPR000472	Activin_recp	Domain
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR045860	Snake_toxin-like_sf	Homologous_superfamily

Pfam: PF00069, PF01064

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor-protein] + ADP + H(+) (RHEA:18673)
• L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor-protein] + ADP + H(+) (RHEA:44880)

UniProt features (63 total): strand 20, helix 15, disulfide bond 5, sequence variant 4, turn 4, sequence conflict 3, glycosylation site 2, topological domain 2, binding site 2, signal peptide 1, chain 1, transmembrane region 1, domain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
2H62	X-RAY DIFFRACTION	1.85
2QLU	X-RAY DIFFRACTION	2
5NGV	X-RAY DIFFRACTION	2
9D20	X-RAY DIFFRACTION	2.67
7MRZ	X-RAY DIFFRACTION	3
9N4K	ELECTRON MICROSCOPY	3.2
7OLY	X-RAY DIFFRACTION	3.27
5NHR	X-RAY DIFFRACTION	3.35
4FAO	X-RAY DIFFRACTION	3.36

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13705-F1	84.18	0.60

Antibody-complex structures (SAbDab): 4 — 5NGV, 5NHR, 7MRZ, 7OLY

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 321 (proton acceptor)

Ligand- & substrate-binding residues (2): 196–204; 217

Disulfide bonds (5): 29–59, 49–77, 84–103, 90–102, 104–109

Glycosylation sites (2): 42, 65

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1181150	Signaling by NODAL
R-HSA-1433617	Regulation of signaling by NODAL
R-HSA-1502540	Signaling by Activin
R-HSA-201451	Signaling by BMP
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-9006936	Signaling by TGFB family members

MSigDB gene sets: 430 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INSULIN_SECRETION, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, GOBP_GROWTH, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_HORMONE_TRANSPORT, GOBP_ARTERY_DEVELOPMENT, USF_C, GOBP_GASTRULATION_WITH_MOUTH_FORMING_SECOND, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, GOBP_CELL_CELL_SIGNALING, GOBP_PANCREAS_DEVELOPMENT

GO Biological Process (42): negative regulation of transcription by RNA polymerase II (GO:0000122), gastrulation with mouth forming second (GO:0001702), kidney development (GO:0001822), lymphangiogenesis (GO:0001946), blood vessel remodeling (GO:0001974), regulation of DNA-templated transcription (GO:0006355), intracellular iron ion homeostasis (GO:0006879), signal transduction (GO:0007165), cell surface receptor protein serine/threonine kinase signaling pathway (GO:0007178), determination of left/right symmetry (GO:0007368), pattern specification process (GO:0007389), mesoderm development (GO:0007498), heart development (GO:0007507), response to glucose (GO:0009749), post-embryonic development (GO:0009791), anterior/posterior pattern specification (GO:0009952), insulin secretion (GO:0030073), negative regulation of ossification (GO:0030279), lung development (GO:0030324), positive regulation of bone mineralization (GO:0030501), BMP signaling pathway (GO:0030509), pancreas development (GO:0031016), activin receptor signaling pathway (GO:0032924), positive regulation of activin receptor signaling pathway (GO:0032927), organ growth (GO:0035265), odontogenesis of dentin-containing tooth (GO:0042475), positive regulation of osteoblast differentiation (GO:0045669), embryonic foregut morphogenesis (GO:0048617), skeletal system morphogenesis (GO:0048705), roof of mouth development (GO:0060021), lymphatic endothelial cell differentiation (GO:0060836), artery development (GO:0060840), venous blood vessel development (GO:0060841), retina vasculature development in camera-type eye (GO:0061298), trophoblast cell migration (GO:0061450), cellular response to growth factor stimulus (GO:0071363), negative regulation of cold-induced thermogenesis (GO:0120163), negative regulation of adipose tissue development (GO:1904178), skeletal system development (GO:0001501), protein phosphorylation (GO:0006468)

GO Molecular Function (15): protein serine/threonine kinase activity (GO:0004674), protein serine/threonine/tyrosine kinase activity (GO:0004712), ATP binding (GO:0005524), activin receptor activity, type II (GO:0016362), activin receptor activity (GO:0017002), kinase activator activity (GO:0019209), growth factor binding (GO:0019838), metal ion binding (GO:0046872), activin binding (GO:0048185), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), transmembrane receptor protein serine/threonine kinase activity (GO:0004675), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (6): cytoplasm (GO:0005737), plasma membrane (GO:0005886), protein-containing complex (GO:0032991), signaling receptor complex (GO:0043235), activin receptor complex (GO:0048179), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by TGFB family members	2
Developmental Biology	1
Signaling by NODAL	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	3
multicellular organism development	2
multicellular organismal process	2
protein kinase activity	2
kinase activity	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
gastrulation	1
renal system development	1
anatomical structure morphogenesis	1
lymph vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
tissue remodeling	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
enzyme-linked receptor protein signaling pathway	1
determination of bilateral symmetry	1
left/right pattern formation	1
tissue development	1
circulatory system development	1
response to hexose	1
regionalization	1
protein secretion	1
peptide hormone secretion	1
ossification	1
regulation of ossification	1
negative regulation of multicellular organismal process	1
respiratory tube development	1
respiratory system development	1
bone mineralization	1

Protein interactions and networks

STRING

2108 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACVR2B	MSTN	O14793	999
ACVR2B	GDF11	O95390	996
ACVR2B	ACVR1B	P36896	988
ACVR2B	TGFBR1	P36897	986
ACVR2B	BMP7	P18075	985
ACVR2B	ACVR2A	P27037	981
ACVR2B	CRIPTO	P13385	968
ACVR2B	ACVR1C	Q8NER5	967
ACVR2B	BMP6	P22004	966
ACVR2B	GDF2	Q9UK05	960
ACVR2B	BMP2	P12643	954
ACVR2B	ACVR1	Q04771	946
ACVR2B	BMP4	P12644	928
ACVR2B	BMPR2	Q13873	923
ACVR2B	CFC1	P0CG37	917

IntAct

65 interactions, top by confidence:

A	B	Type	Score
ALDH3A1	RCCD1	psi-mi:“MI:0914”(association)	0.640
GDF11	ACVR2B	psi-mi:“MI:0407”(direct interaction)	0.590
MSTN	ACVR2B	psi-mi:“MI:0407”(direct interaction)	0.540
ACVR2B	MSTN	psi-mi:“MI:0407”(direct interaction)	0.540
ACVR2B	MSTN	psi-mi:“MI:0915”(physical association)	0.540
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
DLK1	TCAF2	psi-mi:“MI:0914”(association)	0.530
KIR3DL2	METTL15	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
TGFBR2	PIK3R2	psi-mi:“MI:0914”(association)	0.530
CNGA3	C2CD2L	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
IZUMO1	ADCY3	psi-mi:“MI:0914”(association)	0.530
ACVR2B	FSTL1	psi-mi:“MI:0407”(direct interaction)	0.440
ACVR2B	Mstn	psi-mi:“MI:0407”(direct interaction)	0.440
HSP90AB1	ACVR2B	psi-mi:“MI:0915”(physical association)	0.400
ACVR2B	INHBA	psi-mi:“MI:0915”(physical association)	0.400
	AURKA	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AHRR	psi-mi:“MI:0914”(association)	0.350
IZUMO1	CNOT1	psi-mi:“MI:0914”(association)	0.350
RUSF1	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350

BioGRID (131): ACVR2B (Affinity Capture-Western), ACVR2B (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), ACVR2B (Affinity Capture-MS), ACVR2B (Affinity Capture-MS)

ESM2 similar proteins: A1A4I4, C9J798, D4ABX8, O18735, O43374, O75325, O95294, P04629, P06494, P21860, P27040, P29376, P30530, P35739, P38445, P70268, P70424, Q00993, Q06418, Q13641, Q13705, Q16512, Q1WIM1, Q3UFB7, Q4R8Y9, Q5E9Z9, Q5PQV5, Q5RB22, Q5STE3, Q60553, Q61161, Q61526, Q62799, Q63433, Q66T47, Q6GQU6, Q6MZW2, Q6P1C6, Q6PFQ7, Q6PJG9

Diamond homologs: A0A0P0XII1, A0A0R0HPY5, A7J1T2, C0LGD6, C0LGD8, C0LGD9, C0LGG3, C0LGR6, C0LGV0, O00238, O00506, O04086, O35607, O46680, O64556, O65440, P04627, P09560, P0C5E2, P10398, P10533, P14056, P15056, P18161, P20792, P27037, P27038, P27039, P27040, P27041, P27966, P28028, P34908, P36894, P36895, P36896, P36897, P36898, P37023, P37172

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
GDF11	up-regulates	ACVR2B	binding
INHBA	“up-regulates activity”	ACVR2B	binding
ACVR2B	“up-regulates activity”	ACVR1B	phosphorylation
BMP7	up-regulates	ACVR2B	binding
MSTN	“up-regulates activity”	ACVR2B	binding
ACVR2B	“up-regulates activity”	SMAD2	phosphorylation
ACVR2B	“up-regulates activity”	SMAD3	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
activin receptor signaling pathway	5	72.7×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

381 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	216
Likely benign	60
Benign	85

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1024343	NM_001106.4(ACVR2B):c.1148G>A (p.Arg383His)	Likely pathogenic
545541	NM_001106.4(ACVR2B):c.1147C>T (p.Arg383Cys)	Likely pathogenic

SpliceAI

1409 predictions. Top by Δscore:

Variant	Effect	Δscore
3:38477277:T:TA	acceptor_gain	1.0000
3:38477278:G:A	acceptor_gain	1.0000
3:38477283:ACAG:A	acceptor_gain	1.0000
3:38477284:C:G	acceptor_gain	1.0000
3:38477285:A:AG	acceptor_gain	1.0000
3:38477285:AG:A	acceptor_gain	1.0000
3:38477286:G:GC	acceptor_gain	1.0000
3:38477286:GG:G	acceptor_gain	1.0000
3:38477286:GGC:G	acceptor_gain	1.0000
3:38477286:GGCT:G	acceptor_gain	1.0000
3:38477286:GGCTC:G	acceptor_gain	1.0000
3:38477486:C:G	donor_gain	1.0000
3:38477490:GA:G	donor_gain	1.0000
3:38477491:A:AG	donor_gain	1.0000
3:38477491:ATAG:A	donor_loss	1.0000
3:38477492:TAGGT:T	donor_loss	1.0000
3:38477493:AGGT:A	donor_loss	1.0000
3:38477494:GGTAC:G	donor_loss	1.0000
3:38477495:G:GA	donor_loss	1.0000
3:38477496:T:A	donor_loss	1.0000
3:38477859:A:AG	acceptor_gain	1.0000
3:38477860:G:GC	acceptor_gain	1.0000
3:38477860:GGCA:G	acceptor_gain	1.0000
3:38477968:AAGG:A	donor_loss	1.0000
3:38477969:AGGT:A	donor_loss	1.0000
3:38477970:GGTAA:G	donor_loss	1.0000
3:38477971:G:A	donor_loss	1.0000
3:38477972:T:A	donor_loss	1.0000
3:38478138:CAG:C	acceptor_loss	1.0000
3:38478139:A:AG	acceptor_gain	1.0000

AlphaMissense

3337 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:38477319:T:A	C29S	1.000
3:38477320:G:C	C29S	1.000
3:38477321:C:G	C29W	1.000
3:38477409:T:A	C59S	1.000
3:38477409:T:C	C59R	1.000
3:38477410:G:A	C59Y	1.000
3:38477410:G:C	C59S	1.000
3:38477411:C:G	C59W	1.000
3:38477421:T:A	W63R	1.000
3:38477421:T:C	W63R	1.000
3:38477423:G:C	W63C	1.000
3:38477423:G:T	W63C	1.000
3:38477463:T:A	C77S	1.000
3:38477463:T:C	C77R	1.000
3:38477464:G:A	C77Y	1.000
3:38477464:G:C	C77S	1.000
3:38477466:T:A	W78R	1.000
3:38477466:T:C	W78R	1.000
3:38477468:G:C	W78C	1.000
3:38477468:G:T	W78C	1.000
3:38477484:T:A	C84S	1.000
3:38477484:T:C	C84R	1.000
3:38477485:G:A	C84Y	1.000
3:38477485:G:C	C84S	1.000
3:38477485:G:T	C84F	1.000
3:38477486:C:G	C84W	1.000
3:38477868:T:A	C90S	1.000
3:38477868:T:C	C90R	1.000
3:38477869:G:A	C90Y	1.000
3:38477869:G:C	C90S	1.000

dbSNP variants (sampled 300 via entrez): RS1000015367 (3:38461040 C>T), RS1000032827 (3:38455444 C>T), RS1000123974 (3:38480663 T>C), RS1000125991 (3:38487430 G>A), RS1000239473 (3:38487166 C>T), RS1000307373 (3:38466925 A>G), RS1000371639 (3:38483780 G>A,C), RS1000489390 (3:38455691 C>A,G,T), RS1000550863 (3:38470500 G>T), RS1000661629 (3:38471812 G>A), RS1000725504 (3:38490126 C>T), RS1000739674 (3:38454067 C>T), RS1000760378 (3:38453667 T>C,G), RS1000892825 (3:38470127 T>C), RS1000991550 (3:38476296 T>C,G)

Disease associations

OMIM: gene MIM:602730 | disease phenotypes: MIM:613751, MIM:612260, MIM:601144

GenCC curated gene-disease

Disease	Classification	Inheritance
heterotaxy, visceral, 4, autosomal	Strong	Autosomal dominant

Mondo (3): heterotaxy, visceral, 4, autosomal (MONDO:0013403), pyogenic bacterial infections due to MyD88 deficiency (MONDO:0012839), Brugada syndrome (MONDO:0015263)

Orphanet (3): Visceral heterotaxy (Orphanet:450), OBSOLETE: Bacterial susceptibility due to TLR signaling pathway deficiency (Orphanet:183713), Brugada syndrome (Orphanet:130)

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001629	Ventricular septal defect
HP:0001651	Dextrocardia
HP:0001669	Transposition of the great arteries
HP:0001674	Complete atrioventricular canal defect
HP:0001748	Polysplenia
HP:0003577	Congenital onset
HP:0004935	Pulmonary artery atresia
HP:0005160	Total anomalous pulmonary venous return
HP:0006695	Atrioventricular canal defect
HP:0010452	Ectopia of the spleen
HP:0011565	Common atrium
HP:0011671	Interrupted inferior vena cava with azygous continuation
HP:0012020	Right aortic arch
HP:0031348	Dextrotransposition of the great arteries
HP:0033379	Bilateral superior vena cava
HP:0034188	Midline liver

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002457_2	P wave duration	8.000000e-27
GCST007876_48	Estimated glomerular filtration rate	5.000000e-11
GCST008058_63	Estimated glomerular filtration rate	8.000000e-26
GCST008521_5	Bitter beverage consumption	2.000000e-06
GCST010989_215	Body size at age 10	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005094	P wave duration
EFO:0010089	bitter beverage consumption measurement
EFO:0009819	comparative body size at age 10, self-reported

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100
C567379	MYD88 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5466 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 67,474 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL5416410	DASATINIB	4	655
CHEMBL217092	SARACATINIB	3	3,982
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL603469	LESTAURTINIB	3
CHEMBL1090090	VX-702	2	1,045
CHEMBL403989	TG100-801	2	249
CHEMBL1090479	GSK-1070916	1	177
CHEMBL1908397	KW-2449	1	622
CHEMBL2041933	AZD-7762	1	1,240
CHEMBL574738	AST-487	1	451

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Type II receptor serine/threonine kinases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
bimagrumab	Binding	11.76	pKd

Binding affinities (BindingDB)

6 measured of 6 human assays (6 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole	KD	9.8 nM
BMS-354825	KD	27 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S)-3-hydroxy-1-methyl-4-piperidinyl]-1-benzopyran-4-one	KD	5300 nM

ChEMBL bioactivities

39 potent at pChembl≥5 of 39 total, top 34 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	Kd	3.019	nM	CHEMBL5653589
8.34	ED50	4.528	nM	CHEMBL5653589
8.12	Kd	7.6	nM	CHEMBL1241674
8.04	Kd	9.1	nM	CHEMBL386051
8.00	IC50	10	nM	CHEMBL1808264
7.75	IC50	17.9	nM	CHEMBL5591770
7.16	IC50	68.9	nM	CHEMBL5595138
7.04	Kd	92	nM	VX-702
6.60	Kd	253	nM	AZD-7762
6.44	IC50	364	nM	CHEMBL6172244
6.43	Kd	370	nM	KW-2449
6.38	Kd	419	nM	TG100-801
6.24	Kd	570	nM	DASATINIB
6.04	Kd	901	nM	CHEMBL3991933
5.89	Kd	1300	nM	KW-2449
5.85	Kd	1400	nM	AST-487
5.62	Kd	2400	nM	ALVOCIDIB
5.62	Kd	2400	nM	PAZOPANIB
5.61	Kd	2485	nM	DASATINIB
5.50	IC50	3130	nM	CHEMBL4283638
5.50	Kd	3181	nM	CHEMBL3752910
5.50	Kd	3200	nM	PLX-4720
5.42	Kd	3800	nM	LESTAURTINIB
5.41	Kd	3878	nM	SARACATINIB
5.37	Kd	4300	nM	TAE-684
5.34	Kd	4600	nM	STAUROSPORINE
5.32	ED50	4773	nM	CHEMBL3752910
5.32	Kd	4800	nM	SB-202190
5.28	Kd	5200	nM	AXITINIB
5.23	Kd	5900	nM	JNJ-7706621
5.20	IC50	6344	nM	CHEMBL5594704
5.12	IC50	7680	nM	CHEMBL3823101
5.03	IC50	9300	nM	CHEMBL513147
5.00	Kd	9900	nM	GSK-1070916

PubChem BioAssay actives

36 with measured affinity, of 452 total; 29 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147802: Binding affinity to human ACVR2B incubated for 45 mins by Kinobead based pull down assay	kd	0.0030	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624820: Binding constant for ACVR2B kinase domain	kd	0.0076	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624820: Binding constant for ACVR2B kinase domain	kd	0.0091	uM
2,6-difluoro-N-[2-fluoro-5-[5-[2-[(6-morpholin-4-yl-3-pyridinyl)amino]pyrimidin-4-yl]-2-propan-2-yl-1,3-thiazol-4-yl]phenyl]benzenesulfonamide	609684: Inhibition of ACTR-2B	ic50	0.0100	uM
5-(4-acetyl-1H-pyrrol-2-yl)-2-[cyclopropyl-[1-(3-methoxy-4-pyridinyl)pyrazol-4-yl]amino]-1,3-thiazole-4-carboxamide	2112256: Inhibition of ACTR2B (unknown origin) by TR-FRET assay	ic50	0.0179	uM
5-(4-acetyl-1H-pyrrol-2-yl)-2-[cyclopropyl-[1-[3-(hydroxymethyl)-4-pyridinyl]pyrazol-4-yl]amino]-1,3-thiazole-4-carboxamide	2112256: Inhibition of ACTR2B (unknown origin) by TR-FRET assay	ic50	0.0689	uM
6-(N-carbamoyl-2,6-difluoroanilino)-2-(2,4-difluorophenyl)pyridine-3-carboxamide	476304: Binding affinity to ACVR2beta	kd	0.0920	uM
3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-2-carboxamide	1424902: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.2530	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624820: Binding constant for ACVR2B kinase domain	kd	0.3700	uM
[4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenyl] benzoate	1424902: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.4190	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435147: Binding constant for ACVR2B kinase domain	kd	0.5700	uM
3-(2-methyl-1,3-benzoxazol-5-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-4-amine	1424902: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.9010	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	624820: Binding constant for ACVR2B kinase domain	kd	1.4000	uM
Pazopanib	435147: Binding constant for ACVR2B kinase domain	kd	2.4000	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	435147: Binding constant for ACVR2B kinase domain	kd	2.4000	uM
4-[6-[4-(1-pyrrolidin-1-ylethyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]naphthalene-1-sulfonamide	1417564: Inhibition of GST-tagged human ACVR2B catalytic domain (185 to 488 residues) expressed in Baculovirus expression system by LanthaScreen assay	ic50	3.1300	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147802: Binding affinity to human ACVR2B incubated for 45 mins by Kinobead based pull down assay	kd	3.1814	uM
N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide	624820: Binding constant for ACVR2B kinase domain	kd	3.2000	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507822: Binding affinity to ACVR2B	kd	3.8000	uM
N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine	1424902: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	3.8780	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624820: Binding constant for ACVR2B kinase domain	kd	4.3000	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	435147: Binding constant for ACVR2B kinase domain	kd	4.6000	uM
4-[4-(4-fluorophenyl)-5-pyridin-4-yl-1H-imidazol-2-yl]phenol	435147: Binding constant for ACVR2B kinase domain	kd	4.8000	uM
Axitinib	624820: Binding constant for ACVR2B kinase domain	kd	5.2000	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435147: Binding constant for ACVR2B kinase domain	kd	5.9000	uM
5-(4-acetyl-1H-pyrrol-2-yl)-2-[cyclopropyl-[1-(3-fluoro-4-pyridinyl)pyrazol-4-yl]amino]-1,3-thiazole-4-carboxamide	2112256: Inhibition of ACTR2B (unknown origin) by TR-FRET assay	ic50	6.3440	uM
4-[4-[(dimethylamino)methyl]-2,5-dimethoxyphenyl]-2-methyl-2,7-naphthyridin-1-one	1309661: Inhibition of ACVR2B (unknown origin)	ic50	7.6800	uM
4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline	1967380: Inhibition of ACVR2B (unknown origin) by LanthaScreen TR-FRET assay	ic50	9.3000	uM
3-[4-[4-[2-[3-[(dimethylamino)methyl]phenyl]-1H-pyrrolo[2,3-b]pyridin-4-yl]-1-ethylpyrazol-3-yl]phenyl]-1,1-dimethylurea	1424902: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	9.9000	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects reaction, affects expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Glyphosate	decreases expression, increases expression	1
Arsenic	affects expression	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Diclofenac	affects expression	1
Estradiol	decreases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Toluene	decreases expression, increases methylation	1
Tretinoin	decreases expression	1
1-Methyl-4-phenylpyridinium	affects expression, affects reaction	1
Cyclosporine	increases expression	1
Antirheumatic Agents	increases expression	1

ChEMBL screening assays

104 unique, capped per target: 104 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1032241	Binding	Inhibition of ACVR2B at 3 uM	Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. — J Med Chem

Cellosaurus cell lines

11 cell lines: 10 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D2HU	Abcam Raji ACVR2B KO	Cancer cell line	Male
CVCL_D8YN	Ubigene HEK293 ACVR2B KO	Transformed cell line	Female
CVCL_E8IH	Jurkat-NFAT-Luc2-ACVR2B-KO-CD16-V158-OE	Cancer cell line	Male
CVCL_SB38	HAP1 ACVR2B (-) 1	Cancer cell line	Male
CVCL_SB39	HAP1 ACVR2B (-) 2	Cancer cell line	Male
CVCL_SB40	HAP1 ACVR2B (-) 3	Cancer cell line	Male
CVCL_SB41	HAP1 ACVR2B (-) 4	Cancer cell line	Male
CVCL_SB42	HAP1 ACVR2B (-) 5	Cancer cell line	Male
CVCL_SB43	HAP1 ACVR2B (-) 6	Cancer cell line	Male
CVCL_UQ05	Abcam Jurkat ACVR2B KO	Cancer cell line	Male

Clinical trials (associated diseases)

43 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00702117	PHASE4	COMPLETED	Ajmaline Utilization in the Diagnosis and Treatment of Cardiac Arrhythmias
NCT00701077	PHASE3	TERMINATED	DAPERB 3,4-DiAminoPyridine and Electrophysiological Response in Brugada Syndrome
NCT00927732	PHASE3	TERMINATED	Hydroquinidine Versus Placebo in Patients With Brugada Syndrome
NCT02933437	PHASE2	UNKNOWN	The Response To Ajmaline Provocation in Healthy Subjects
NCT07146880	PHASE2	NOT_YET_RECRUITING	Empagliflozin as a Potential Therapeutic Solution for Patients With Brugada Syndrome
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT02014961	Not specified	UNKNOWN	Worm Study: Modifier Genes in Sudden Cardiac Death
NCT02052765	Not specified	COMPLETED	AnalyST & Brugada Syndrome - Feasibility Study
NCT02302274	Not specified	COMPLETED	Diagnostic Value and Safety of Flecainide Infusion Test in Brugada Syndrome
NCT02344277	Not specified	COMPLETED	Evaluation of Subcutaneous Implantable Cardiac Defibrillator in Brugada Patients
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02641431	Not specified	COMPLETED	Epicardial Ablation in Brugada Syndrome
NCT02704416	Not specified	COMPLETED	Ablation in Brugada Syndrome for the Prevention of VF
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03435393	Not specified	UNKNOWN	Ripple Mapping for Epicardial Mapping of Brugada Syndrome
NCT03485508	Not specified	UNKNOWN	The Brugada Syndrome: a Follow-up Study
NCT03491475	Not specified	UNKNOWN	Echocardiography During Ajmaline Test
NCT03524079	Not specified	COMPLETED	Right Ventricle Morphology and Hemodynamics in BrS
NCT03764592	Not specified	COMPLETED	VF Mapping in Brugada and Early Repolarization Syndromes
NCT03775954	Not specified	RECRUITING	Fetal Electrophysiologic Abnormalities in High-Risk Pregnancies Associated With Fetal Demise
NCT03992677	Not specified	COMPLETED	Feasibility of Improving Risk Stratification in Brugada Syndrome
NCT04124237	Not specified	COMPLETED	Long Term Monitoring for Risk of Sudden Death
NCT04232787	Not specified	UNKNOWN	Southeast Asian Brugada Syndrome Cohort
NCT04257994	Not specified	RECRUITING	Distribution of Cell-cell Junction Proteins in Arrhythmic Disorders
NCT04420078	Not specified	COMPLETED	Brugada Ablation of VF Substrate Ongoing MultiCenter Registry
NCT04580992	Not specified	UNKNOWN	Defining the Electrocardiographic Effect of Propofol on the Ajmaline Provocation Drug Challenge: A Prospective Trial
NCT04650009	Not specified	COMPLETED	Physical Activity in Children With Inherited Cardiac Diseases
NCT04712136	Not specified	COMPLETED	Healthy-related Quality of Life and Physical Activity of Children With Cardiac Malformations
NCT04808193	Not specified	UNKNOWN	European Perioperative Brugada Survey
NCT05048602	Not specified	UNKNOWN	Drug-induced Brugada Syndrome Research Database
NCT05274646	Not specified	COMPLETED	Impact on Risk Stratification of Overlap Syndrome Phenotype in Patients With E1784K Mutation in SCN5A
NCT05283759	Not specified	RECRUITING	UZ Brussel HRMC Registry of Brugada Syndrome
NCT05521451	Not specified	RECRUITING	Clinical Cohort Study - TRUST
NCT05643209	Not specified	RECRUITING	Brugada Syndrome Substrate Characterization and Ablation
NCT05685134	Not specified	COMPLETED	Epicardial Radiofrequency Catheter Ablation in Patients With Brugada Syndrome
NCT06376552	Not specified	COMPLETED	Artificial Intelligence for the Prioritization of Genetic Background in Brugada Syndrome
NCT06546137	Not specified	RECRUITING	National Network for Cardiovascular Genomics: Advancing Cardiovascular Healthcare for Hereditary Diseases in Brazil’s Unified Health System Through a Multicenter Registry
NCT06567639	Not specified	COMPLETED	High Density Mapping in Brugada Syndrome
NCT06647927	Not specified	RECRUITING	GenLab: Unveiling the Genetic Landscape of Brugada Syndrome: Novel Biomarker Discovery for Precise Diagnosis
NCT06653504	Not specified	COMPLETED	The Conus Brugada Syndrome Study